Introduction
Disclosures
Timeline
2003: Discovery PCSK9 Mutations
2003: PCSK9 Mutations Cause Dominant LDL
2004: Overexpression of PCSK9 Eliminates LDLRs
2004: Normal Function of PCSK9
Do LOF Mutations in PCSK9 Lower LDL
LOF Mutations in PCSK9 Lower LDL-C
2005: Plasma Cholesterol Levels Reduced
PCSK9 Mutations: A Tool to Test
Mendelian Randomization
2006: LOF Mutations in PCSK9 Lower CHD
LDL-Lowering and Reduction in CHD
Genotypes Capture Another Dimension: Time
PCSK9: From Genes to Public Health
A Healthy Woman with No PCSK9
PCSK9: New Target for LDL-Lowering
PCSK9: Target for LDL-Lowering
2006: PCSK9 acts extracellularly
PCSK9 Promotes LDLR Degradation in Hepatocytes
PCSK9 Crystal Structure
PCSK9 & LDL Receptor
Therapeutic Approaches to Inhibit PCSK9 Action
Three Studies 2007-2009
2012 First Monoclonal Antibody in Humans
Evolocumab in Patients with Hypercholesterolemia
Alirocumab + Statin in Patients
siRNA to Silence PCSK9
PCSK9: Discovery to Clinical Trials in 7 Years
JCC Seminars: Discovery to History in 7 Years
Human Genetics & Translation
Is PCSK9 Paradigmatic or Exceptional?
2009: Dallas Heart Study
2010: Mutations in ANGPTL3 Cause Hypolipidemia
Complex Diseases Are Not Necessarily So Complex
Collaborators / Thank You
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